scholarly journals Selectivity among anti-σ factors by Mycobacterium tuberculosis ClpX influences intracellular levels of Extracytoplasmic Function σ factors

2018 ◽  
Author(s):  
Anuja C Joshi ◽  
Prabhjot Kaur ◽  
Radhika Nair ◽  
Deepti Lele ◽  
Vinay Kumar Nandicoori ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mycobacterium Tuberculosis ◽  
Point Mutation ◽  
Dwell Time ◽  
Σ Factor ◽  
Small Stable Rna ◽  
Order Of Magnitude ◽  
Energy Dependent ◽  
Magnitude Difference

Extracytoplasmic Function σ factors that are stress inducible are often sequestered in an inactive complex with a membrane-associated anti-σ factor. M. tuberculosis membrane-associated anti-σ factors have a small stable RNA gene A-like degron for targeted proteolysis. Interaction between the unfoldase, ClpX, and the substrate with an accessible degron initiates energy-dependent proteolysis. Four anti-σ factors with a mutation in the degron provided a set of natural substrates to evaluate the influence of the degron on degradation strength in ClpX-substrate processivity. We note that a point mutation in the degron (XXX-Ala-Ala) leads to an order of magnitude difference in the dwell time of the substrate on ClpX. Differences in ClpX/anti-σ; interactions were correlated with change in unfoldase activity. GFP chimeras or polypeptides of identical length with the anti-σ degron also demonstrate degron-dependent variation in ClpX activity. We show that degron-dependent ClpX activity leads to differences in anti-σ factor degradation thereby regulating the release of free σ from the σ/anti-σ complex. M. tuberculosis ClpX activity thus influences changes in gene expression by modulating the cellular abundance of ECF σ factors.

scholarly journals Selectivity among Anti-σ Factors byMycobacterium tuberculosisClpX Influences Intracellular Levels of Extracytoplasmic Function σ Factors

2019 ◽  
Vol 201 (6) ◽  
Author(s):  
Anuja C. Joshi ◽  
Prabhjot Kaur ◽  
Radhika K. Nair ◽  
Deepti S. Lele ◽  
Vinay Kumar Nandicoori ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mycobacterium Tuberculosis ◽  
Point Mutation ◽  
Fluorescent Protein ◽  
Content Type ◽  
Environmental Stimuli ◽  
Σ Factor ◽  
Small Stable Rna ◽  
Order Of Magnitude ◽  
Green Fluorescent

ABSTRACTExtracytoplasmic function σ factors that are stress inducible are often sequestered in an inactive complex with a membrane-associated anti-σ factor.Mycobacterium tuberculosismembrane-associated anti-σ factors have a small, stable RNA gene A (ssrA)-like degron for targeted proteolysis. Interaction between the unfoldase, ClpX, and a substrate with an accessible degron initiates energy-dependent proteolysis. Four anti-σ factors with a mutation in the degron provided a set of natural substrates to evaluate the influence of the degron on degradation strength in ClpX-substrate processivity. We note that a point mutation in the degron (X-Ala-Ala) leads to an order-of-magnitude difference in the dwell time of the substrate on ClpX. Differences in ClpX/anti-σ interactions were correlated with changes in unfoldase activities. Green fluorescent protein (GFP) chimeras or polypeptides with a length identical to that of the anti-σ factor degron also demonstrate degron-dependent variation in ClpX activities. We show that degron-dependent ClpX activity leads to differences in anti-σ degradation, thereby regulating the release of free σ from the σ/anti-σ complex.M. tuberculosisClpX activity thus influences changes in gene expression by modulating the cellular abundance of ECF σ factors.IMPORTANCEThe ability ofMycobacterium tuberculosisto quickly adapt to changing environmental stimuli occurs by maintaining protein homeostasis. Extracytoplasmic function (ECF) σ factors play a significant role in coordinating the transcription profile to changes in environmental conditions. Release of the σ factor from the anti-σ is governed by the ClpXP2P1 assembly.M. tuberculosisECF anti-σ factors have anssrA-like degron for targeted degradation. A point mutation in the degron leads to differences in ClpX-mediated proteolysis and affects the cellular abundance of ECF σ factors. ClpX activity thus synchronizes changes in gene expression with environmental stimuli affectingM. tuberculosisphysiology.

scholarly journals The simplest mathematical model of consciousness

2014 ◽  
Author(s):  
Rodrick Wallace
Keyword(s):  
Gene Expression ◽  
Mathematical Model ◽  
Cognitive Process ◽  
Arrhenius Relation ◽  
Neural Tissues ◽  
Global Workspace ◽  
Order Of Magnitude ◽  
Information Treatment ◽  
Magnitude Difference ◽  
Magnitude Increase

Adaptation of the Arrhenius relation to cognitive process explains how an order of magnitude difference in the rate of metabolic free energy metabolism for neural tissues translates into many orders of magnitude increase in the rate of assembling sets of cognitive submodules into the temporary, tunable, 'global workspace' coalitions of consciousness, much faster than such closely analogous processes as wound healing, immune response, and gene expression. The model strongly contradicts Tononi's 'panpsychic' integrated information treatment of consciousness.

scholarly journals The simplest mathematical model of consciousness

2014 ◽  
Author(s):  
Rodrick Wallace
Keyword(s):  
Gene Expression ◽  
Mathematical Model ◽  
Cognitive Process ◽  
Arrhenius Relation ◽  
Neural Tissues ◽  
Global Workspace ◽  
Order Of Magnitude ◽  
Information Treatment ◽  
Magnitude Difference ◽  
Magnitude Increase

Adaptation of the Arrhenius relation to cognitive process explains how an order of magnitude difference in the rate of metabolic free energy metabolism for neural tissues translates into many orders of magnitude increase in the rate of assembling sets of cognitive submodules into the temporary, tunable, 'global workspace' coalitions of consciousness, much faster than such closely analogous processes as wound healing, immune response, and gene expression. The model strongly contradicts Tononi's 'panpsychic' integrated information treatment of consciousness.

TEM Studies and Contact Resistance of Au/Ni/Ti/Ta/n-GaN Ohmic Contacts

2003 ◽  
Vol 764 ◽  
Author(s):  
D.N. Zakharov ◽  
Z. Liliental-Weber ◽  
A. Motayed ◽  
S.N. Mohammad
Keyword(s):  
Contact Resistance ◽  
Ohmic Contacts ◽  
High Resolution Electron Microscopy ◽  
X Ray ◽  
Electron Energy Loss Spectrometry ◽  
Resolution Electron ◽  
Order Of Magnitude ◽  
Contact Surfaces ◽  
Electron Energy Loss ◽  
Magnitude Difference

AbstractOhmic Ta/Ti/Ni/Au contacts to n-GaN have been studied using high resolution electron microscopy (HREM), energy dispersive X-ray spectrometry (EDX) and electron energy loss spectrometry (EELS). Two different samples were used: A - annealed at 7500C withcontact resistance 5×10-6 Ω cm2 and B-annealed at 7750C with contact resistance 6×10-5 Ω cm2. Both samples revealed extensive in- and out-diffusion between deposited layers with some consumption ofGaNlayerand formation of TixTa1-xN50 (0<x<25) at the GaN interface. Almost an order of magnitude difference in contact resistances can be attributed to structure and chemical bonding of Ti-O layers formed on the contact surfaces.

scholarly journals Relationship between rifampin MICs for and rpoB mutations of Mycobacterium tuberculosis strains isolated in Japan.

1996 ◽  
Vol 40 (4) ◽  
pp. 1053-1056 ◽  
Author(s):  
H Ohno ◽  
H Koga ◽  
S Kohno ◽  
T Tashiro ◽  
K Hara
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Point Mutation ◽  
Rpob Gene ◽  
The Other ◽  
Clinical Isolates ◽  
Sequencing Analysis ◽  
The Relationship

We analyzed the relationship between rifampin MICs and rpoB mutations of 40 clinical isolates of Mycobacterium tuberculosis. A point mutation in either codon 516, 526, or 531 was found in 13 strains requiring MICs of > or = 64 micrograms/ml, while 21 strains requiring MICs of < or = 1 microgram/ml showed no alteration in these codons. However, 3 of these 21 strains contained a point mutation in either codon 515 or 533. Of the other six strains requiring MICs between 2 and 32 micrograms/ml, three contained a point mutation in codon 516 or 526, while no alteration was detected in the other three. Our results indicate that the sequencing analysis of a 69-bp fragment in the rpoB gene is useful in predicting rifampin-resistant phenotypes.

scholarly journals Moxifloxacin Activates the SOS Response in Mycobacterium tuberculosis in a Dose- and Time-Dependent Manner

2021 ◽  
Vol 9 (2) ◽  
pp. 255
Author(s):  
Angelo Iacobino ◽  
Giovanni Piccaro ◽  
Manuela Pardini ◽  
Lanfranco Fattorini ◽  
Federico Giannoni
Keyword(s):  
Gene Expression ◽  
Mycobacterium Tuberculosis ◽  
Physiological State ◽  
Transcriptional Response ◽  
Sos Response ◽  
Resistant Mutant ◽  
Time Dependent ◽  
Dependent Manner ◽  
Gyra Gene ◽  
Drug Concentrations

Previous studies on Escherichia coli demonstrated that sub-minimum inhibitory concentration (MIC) of fluoroquinolones induced the SOS response, increasing drug tolerance. We characterized the transcriptional response to moxifloxacin in Mycobacterium tuberculosis. Reference strain H37Rv was treated with moxifloxacin and gene expression studied by qRT-PCR. Five SOS regulon genes, recA, lexA, dnaE2, Rv3074 and Rv3776, were induced in a dose- and time-dependent manner. A range of moxifloxacin concentrations induced recA, with a peak observed at 2 × MIC (0.25 μg/mL) after 16 h. Another seven SOS responses and three DNA repair genes were significantly induced by moxifloxacin. Induction of recA by moxifloxacin was higher in log-phase than in early- and stationary-phase cells, and absent in dormant bacilli. Furthermore, in an H37Rv fluoroquinolone-resistant mutant carrying the D94G mutation in the gyrA gene, the SOS response was induced at drug concentrations higher than the mutant MIC value. The 2 × MIC of moxifloxacin determined no significant changes in gene expression in a panel of 32 genes, except for up-regulation of the relK toxin and of Rv3290c and Rv2517c, two persistence-related genes. Overall, our data show that activation of the SOS response by moxifloxacin, a likely link to increased mutation rate and persister formation, is time, dose, physiological state and, possibly, MIC dependent.

scholarly journals Significant contribution of the CmeABC Efflux pump in high-level resistance to ciprofloxacin and tetracycline in Campylobacter jejuni and Campylobacter coli clinical isolates

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Saeed Sharifi ◽  
Bita Bakhshi ◽  
Shahin Najar-peerayeh
Keyword(s):  
Gene Expression ◽  
Point Mutation ◽  
Campylobacter Jejuni ◽  
Significant Contribution ◽  
Efflux Pump ◽  
Campylobacter Coli ◽  
Rapd Pcr ◽  
Resistant Strains ◽  
High Level ◽  
Level Resistance

Abstract Background Campylobacter resistance to antimicrobial agents is regarded as a major concern worldwide. The aim of this study was to investigate the expression of the CmeABC efflux pump and the RAPD-PCR pattern in drug-resistant Campylobacter isolates. Methods A total of 283 stool specimens were collected from children under the age of five with diarrhea. The minimum inhibitory concentration (MIC) of tetracycline and ciprofloxacin was determined by broth microdilution method and E-test, respectively. Detection of tetracycline and ciprofloxacin determinants was done by amplification of tetO gene and PCR-sequencing of the gyrA gene. The cmeABC transcriptional expression was analyzed by Real-time (RT)-PCR. Clonal correlation of resistant strains was determined by RAPD-PCR genotyping. Results Out of 283 fecal samples, 20 (7.02%) samples were positive for Campylobacter spp. Analysis of duplex PCR assay of the cadF gene showed that 737 and 461 bp amplicons were corresponding to Campylobacter jejuni and Campylobacter coli, respectively. All of the 17 phenotypically tetracycline-resistant Campylobacter isolates harbored the tetO gene. Also, four phenotypically ciprofloxacin-resistant Campylobacter isolates had a point mutation at codon 257 of the gyrA gene (ACA to ATA; Thr > Ile). High-level expression of the cmeA gene was observed in ciprofloxacin-resistant and high-level tetracycline-resistant Campylobacter isolates, suggesting a positive correlation between the cmeA gene expression level and tetracycline resistance level. Moreover, a statistically significant difference was observed in the cmeA gene expression between ciprofloxacin-resistant and ciprofloxacin-susceptible strains, which signifies the crucial contribution of the efflux pump in conferring multiple drug resistance phenotype among Campylobacter spp. RAPD analysis of Campylobacter isolates exhibited 16 different patterns. Simpsone`s diversity index of RAPD-PCR was calculated as 0.85, showing a high level of homogeneity among the population; however, no clear correlation was detected among tetracycline and/or ciprofloxacin resistant isolates. Conclusion Significant contribution of the CmeABC efflux pump in conferring high-level resistance to tetracycline and ciprofloxacin was observed in C. jejuni and C. coli clinical isolates. The resistant phenotype is suggested to be mediated by CmeABC efflux pumps, the tetO gene, and point mutation of the gyrA gene. Genotyping revealed no clonal correlation among resistant strains, indicating distinct evolution of tetracycline and ciprofloxacin resistant genotypes among the isolates.

Evaluation of efflux pump gene expression among drug susceptible and drug resistant strains of Mycobacterium tuberculosis from Iran

2015 ◽  
Vol 36 ◽  
pp. 23-26 ◽  
Author(s):  
Jalil Kardan Yamchi ◽  
Mehri Haeili ◽  
Seifu Gizaw Feyisa ◽  
Hossein Kazemian ◽  
Abdolrazagh Hashemi Shahraki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mycobacterium Tuberculosis ◽  
Efflux Pump ◽  
Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

scholarly journals The Mycobacterium tuberculosis sRNA F6 regulates expression of groEL/S

2020 ◽  
Author(s):  
Joanna Houghton ◽  
Angela Rodgers ◽  
Graham Rose ◽  
Kristine B. Arnvig
Keyword(s):  
Gene Expression ◽  
Mycobacterium Tuberculosis ◽  
Small Rnas ◽  
Transcriptional Control ◽  
Cold Shock ◽  
Control Of Gene Expression ◽  
Rna Biology ◽  
Mouse Model Of Infection

ABSTRACTAlmost 140 years after the identification of Mycobacterium tuberculosis as the etiological agent of tuberculosis, important aspects of its biology remain poorly described. Little is known about the role of post-transcriptional control of gene expression and RNA biology, including the role of most of the small RNAs (sRNAs) identified to date. We have carried out a detailed investigation of the M. tuberculosis sRNA, F6, and show it to be dependent on SigF for expression and significantly induced during in vitro starvation and in a mouse model of infection. However, we found no evidence of attenuation of a ΔF6 strain within the first 20 weeks of infection. A further exploration of F6 using in vitro models of infection suggests a role for F6 as a highly specific regulator of the heat shock repressor, HrcA. Our results point towards a role for F6 during periods of low metabolic activity similar to cold shock and associated with nutrient starvation such as that found in human granulomas in later stages of infection.

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